cells and tissues - wiley · 2019. 12. 28. · 1 cells and tissues the cell is the basic unit of...

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CELLS AND TISSUES

The cell is the basic unit of life. Microorganisms suchas bacteria, yeast, and amoebae exist as single cells. Bycontrast, the adult human is made up of about 30 trillioncells (1 trillion = 1012) which are mostly organized intocollectives called tissues. Cells are, with a few notableexceptions, small (Fig. 1.1) with dimensions measuredin micrometers (μm, 1μm = 1/1000 mm) and theirdiscovery stemmed from the conviction of a small groupof seventeenth-century microscope makers that a new andundiscovered world lay beyond the limits of resolution ofthe human eye. These pioneers set in motion a science andan industry that continues to the present day.

The first person to observe and record cells was RobertHooke (1635–1703) who described the cella (open spaces)of plant tissues. But the colossus of this era of discoverywas a Dutchman, Anton van Leeuwenhoek (1632–1723), aman with no scientific training but with unrivaled talents asboth a microscope maker and as an observer and recorder ofthe microscopic living world. van Leeuwenhoek was a con-temporary and friend of the Delft artist Johannes Vermeer(1632–1675) who pioneered the use of light and shade inart at the same time that van Leeuwenhoek was exploringthe use of light to discover the microscopic world. Despitevan Leeuwenhoek’s efforts, which included the discoveryof microorganisms and protozoa, red blood cells and sper-matozoa, it was to be another 150 years before, in 1838,the botanist Matthias Schleiden and the zoologist TheodorSchwann formally proposed that all living organisms arecomposed of cells. Their “cell theory”, which nowadaysseems so obvious, was a milestone in the development

Cell Biology: A Short Course, Third Edition. Stephen R. Bolsover, Jeremy S. Hyams, Elizabeth A. Shephard and Hugh A. White.© 2011 John Wiley & Sons, Inc. Published 2011 by John Wiley & Sons, Inc.

of modern biology. Nevertheless general acceptance tookmany years, in large part because the plasma membrane(Fig. 1.2), the membrane surrounding the cell that dividesthe living inside from the nonliving extracellular medium,is too thin to be seen using a light microscope.

PRINCIPLES OF MICROSCOPY

Microscopes make small objects appear bigger. A lightmicroscope will magnify an image up to 1500 times itsoriginal size. Electron microscopes can achieve magnifi-cations up to several million times. However, bigger isonly better when more details are revealed. The fineness ofdetail that a microscope can reveal is its resolving power.This is defined as the smallest distance that two objects canapproach one another yet still be recognized as being sep-arate. The resolution that a microscope achieves is mainlya function of the wavelength of the illumination sourceit employs. The smaller the wavelength, the smaller theobject that will cause diffraction, and the better the resolv-ing power. The light microscope, because it uses visiblelight of wavelength around 500 nanometers (nm; 1 nm =1/1000 μm), can distinguish objects as small as about halfthis: 250 nm. It can therefore be used to visualize the small-est cells and the major intracellular structures or organelles.The microscopic study of cell structure and organization isknown as cytology. An electron microscope is required toreveal the ultrastructure (the fine detail) of the organellesand other intracellular structures (Fig. 1.2). The wavelength

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2 CHAPTER 1 CELLS AND TISSUES

Yeast 5 µm Human cell20 µm

Most eukaryotic cells are in the range 5 µm–100 µm

Frog egg 1 mm

Some exceptional cells can be seen with the naked eye

Ciliates0.25 mm(250 µm)

Prokaryotes are the smallest true cells. Most are 1–2 µm

Viruses are submicroscopic particles 50–100 nm

Figure 1.1. Dimensions of some example cells. 1 mm = 10−3 m; 1 μm = 10−6 m; 1 nm = 10−9 m.

of an electron beam is about 100,000 times less than that ofwhite light. In theory, this should lead to a correspondingincrease in resolution. In practice, the transmission type ofelectron microscope can distinguish structures about 1000times smaller than is possible in the light microscope, thatis, down to about 0.2 nm in size.

The Light Microscope

A light microscope (Figs. 1.3A and 1.4) consists of a lightsource, which may be the sun or an artificial light, plusthree glass lenses: a condenser lens to focus light on thespecimen, an objective lens to form the magnified image,and a projector lens, usually called the eyepiece, to con-vey the magnified image to the eye. Depending on the focallength of the various lenses and their arrangement, a givenmagnification is achieved. In bright-field microscopy, theimage that reaches the eye consists of the colors of white

light minus those absorbed by the cell. Most living cellshave little color and are therefore largely transparent totransmitted light. This problem can be overcome by cyto-chemistry, the use of colored stains to selectively high-light particular structures and organelles. However, manyof these compounds are highly toxic and to be effectivethey often require that the cell or tissue is subjected to aseries of harsh chemical treatments. A different approach,and one that can be applied to living cells, is the use ofphase-contrast microscopy. This relies on the fact thatlight travels at different speeds through regions of the cellthat differ in composition. The phase-contrast microscopeconverts these differences in refractive index into differ-ences in contrast, and considerably more detail is revealed(Fig. 1.5). Light microscopes come in a number of phys-ical orientations (upright, inverted, etc.) but whatever theorientation of the microscope, the optical principles are thesame.

Example 1.1 Sterilization by Filtration

Because even the smallest cells are larger than 1 μm,harmful bacteria and other organisms can be removedfrom drinking water by passing through a filter with200 nm diameter holes. Filters can vary in size fromhuge, such as those used in various commercial

processes, to small enough to be easily transportable bybackpackers. Filtering drinking water greatly reducesthe chances of bringing back an unwanted souvenirfrom your camping trip!

PRINCIPLES OF MICROSCOPY 3

Nucleolus

Nucleus

Mitochondrion

Mitochondrion

Mitochondrial ribosome

Golgi apparatus

Nuclear envelope

Nuclear pore

Centrosome

Microtubule

Rough endoplasmic reticulum

Vesicle

Smooth endoplasmic reticulum

Cytoplasm

Heterochromatin

Plasma membrane

Actinfilaments

10 µm

10 µm

Internalmembranes

Intermediatefilaments

Peroxisome

Lysosome

Cytoplasmic ribosome

Structures revealed inlight microscope image

Structures revealed inelectron microscope image

Figure 1.2. Cell structure as seen through the light and transmission electron microscopes.

The Electron Microscope

The most commonly used type of electron microscope inbiology is called the transmission electron microscopebecause electrons are transmitted through the specimen tothe observer. The transmission electron microscope hasessentially the same design as a light microscope, but thelenses, rather than being glass, are electromagnets that bendbeams of electrons (Fig. 1.3B). An electron gun generatesa beam of electrons by heating a thin, V-shaped pieceof tungsten wire to 3000◦C. A large voltage acceleratesthe beam down the microscope column, which is undervacuum because the electrons are slowed and scattered

if they collide with air molecules. The magnified imagecan be viewed on a fluorescent screen that emits lightwhen struck by electrons. While the electron microscopeoffers great improvements in resolution, electron beamsare potentially highly destructive, and biological materialmust be subjected to a complex processing schedule beforeit can be examined. The preparation of cells for electronmicroscopy is summarized in Figure 1.6. The transmissionelectron microscope produces a detailed image but one thatis static, two-dimensional, and highly processed (Fig. 1.7).Often, only a small region of what was once a dynamic,living, three-dimensional cell is revealed. Moreover, the


A Light microscope B Transmission electronmicroscope

Condenser lens

LightLight

Camera

Electrons

Electronsource

Objective lens

Projector lens

Display monitor

Imageprocessingcomputersystem

Imageprojected onfluorescentscreen

Specimen

Lightsource

Condenser lens

Objective lens

Light

Mirrorintroducedfor directviewingby eye

Display monitor


Projectorlens

Imagevieweddirectly

Specimen

Camera

Detector

Lens

Reflectedelectrons

Electrons

Electronsource

Lens

Beam scanner

Specimen

C Scanning electronmicroscope

Display monitor


Figure 1.3. Basic design of light and electron microscopes.

Projector lenses (eyepieces)

Objective lens

Specimen holder

Condenser lens

Light source

Focussing system

Figure 1.4. A simple upright light microscope.

picture revealed is essentially a snapshot taken at theparticular instant that the cell was killed. Clearly,such images must be interpreted with great care. Also,electron microscopes are large, expensive and require askilled operator. Nevertheless, they are the main sourceof information on the ultrastructure of the cell at thenanometer scale.

The Scanning Electron Microscope

Whereas the image in a transmission electron microscopeis formed by electrons transmitted through the specimen,in the scanning electron microscope it is formed fromelectrons that are reflected back from the surface of a spec-imen as the electron beam scans rapidly back and forth

PRINCIPLES OF MICROSCOPY 5

Figure 1.5. Human blood cellsviewed by bright-field (A) and phase-contrast (B) light microscopy. Thin exten-sions of the white blood cell are clear inthe phase contrast image but invisible inthe bright field image. (C) and (D) arephase contrast images acquired 2 and 5minutes after addition of a formyl methio-nine peptide (see page 128). The whiteblood cell is activated and begins crawlingto the right.

After addition of a formyl-methionine peptide

Bright field

A B

C D

Phase contrast

White bloodcell

Red blood cells

After 2 minutes After 5 minutes

10 µm

Figure 1.6. Preparation of tissue forelectron microscopy.

A small piece of tissue (~1 mm3) is immersed in glutaraldehyde and osmium tetroxide. These chemicals bind all the component parts of the cells together; the tissue is said to be fixed. It is then washed thoroughly.

The tissue is dehydrated by soaking in acetone or ethanol.

The tissue is embedded in resin which is then baked hard.

Sections (thin slices less than 100 nm thick) are cut with a machine called an ultramicrotome.

The sections are placed on a small copper grid and stained with uranyl acetate and lead citrate. When viewed in the electron microscope, regions that have bound lots of uranium and lead will appear dark because they are a barrier to the electron beam.

over it (Fig. 1.3C). These reflected electrons are detectedand used to generate a picture on a display monitor.The scanning electron microscope operates over a widemagnification range, from 10 times to 100,000 times, andhas a wide depth of focus. The images created give an

excellent impression of the three-dimensional shape ofobjects (Fig. 1.8). The scanning electron microscope istherefore particularly useful for providing topographicalinformation on the surfaces of cells or tissues. Moderninstruments have a resolution of about 1 nm.


IN DEPTH 1.1 FLUORESCENCE MICROSCOPY

Objective lens

Arclamp

Projectorlens

Camera

Display monitor

Excitationfilter

Dichroicmirror


Specimen

Emissionfilter

Mirrorintroduced

for directviewing

by eye

Imagevieweddirectly

A B

C

D

E

Fluorescent molecules emit light when they areilluminated with light of a shorter wavelength. Familiarexamples are the hidden signature in bank passbooks,which is written in fluorescent ink that glows blue(wavelength about 450 nm) when illuminated withultraviolet light (UV) (wavelength about 360 nm), andthe whitener in fabric detergents that causes your whiteshirt to glow blue when illuminated by the ultravioletlight in a club. The fluorescent dye Hoechst 33342 hasa similar wavelength dependence: it is excited by UVlight and emits blue light. However, it differs from thedyes used in ink or detergent in that it binds tightly tothe DNA in the nucleus and only fluoresces when sobound. Diagram A shows the optical path through amicroscope set up so as to look at a preparation stained

with Hoechst. White light from an arc lamp passesthrough an excitation filter that allows only UV light topass. This light then strikes the heart of the fluorescentmicroscope: a special mirror called a dichroic mirrorthat reflects light of wavelengths shorter than a designedcutoff but transmits light of longer wavelength. To viewHoechst, we use a dichroic mirror of cutoff wavelength400 nm, which therefore reflects the UV excitation lightup through the objective lens and onto the specimen.Any Hoechst bound to DNA in the preparation willemit blue light. Some of this will be captured by theobjective lens and, because its wavelength is greaterthan 400 nm, will not be reflected by the dichroic mirrorbut will instead pass through. An emission filter, set topass only blue light, cuts out any scattered UV light.

ONLY TWO TYPES OF CELL 7

The blue light now passes to the eye or camera in theusual way. Image B shows a field of cells cultured fromrat brain after staining with Hoechst. Only the nucleiare seen, as bright ovals.

Although some of the structures and chemicals foundin cells can be selectively stained by specific fluores-cent dyes, others are most conveniently revealed by usingantibodies. In this technique an animal (usually a mouse,rabbit, or goat) is injected with a protein or other chem-ical of interest. The animal’s immune system recognizesthe chemical as foreign and generates antibodies that bindto (and therefore help neutralize) the chemical. Someblood is then taken from the animal and the antibodiespurified. The antibodies can then be labeled by attach-ing a fluorescent dye. Images C and D show the samefield of brain cells but with the excitation filter, dichroicmirror, and emission filter changed so as to reveal inC a protein called ELAV that is found only in nervecells; and in D, an intermediate filament protein (page291) found only in glial cells. The antibody that bindsto ELAV is labeled with a fluorescent dye that is excitedby blue light and emits green light. The antibody thatbinds to the glial filaments is labeled with a dye thatis excited by green light and emits red light. Becausethese wavelength characteristics are different, the loca-tion of the three chemicals—DNA, ELAV, and inter-mediate filament—can be revealed independently in thesame specimen. Image E shows the previous three imagessuperimposed.

The technique just described is primary immuno-fluorescence and requires that the antibody to the chem-ical of interest be labeled with a dye. Only antibodies to

chemicals that many laboratories study are so labeled. Inorder to reveal other chemicals, scientists use secondaryimmunofluorescence. In this approach, a commercialcompany injects an animal (e.g., a goat) with an anti-body from another animal (e.g., a rabbit). The goat thenmakes “goat anti-rabbit” antibody. This, the secondaryantibody, is purified and labeled with a dye. All the sci-entist has to do is make or buy a rabbit antibody thatbinds to the chemical of interest. No further modifica-tion of this specialized primary antibody is necessary.Once the primary antibody has bound to the specimenand excess antibody rinsed off, the specimen is thenexposed to the fluorescent secondary antibody that bindsselectively to the primary antibody. Viewing the stainedpreparation in a fluorescence microscope then reveals thelocation of the chemical of interest. The same dye-labeledsecondary antibody can be used in other laboratories orat other times to reveal the location of many differentchemicals because the specificity is determined by theunlabeled primary antibody.

A completely different approach uses geneticallyencoded fluorescent molecules. The first to be used wasgreen fluorescent protein from the jellyfish Aequoreavictoria . Cells can be induced to make this protein andthe living cell viewed by fluorescence microscopy. If thecell is induced to make a chimaeric protein comprisinggreen fluorescent protein fused to some or all of aprotein of interest, then fluorescence microscopy canbe used to follow the changing location of this proteinwithin a living cell (e.g., Fig. 18.13 on page 310).Green fluorescent protein is described in more detaillater (pages 115, 148)�.

ONLY TWO TYPES OF CELL

Superficially at least, cells exhibit a staggering diversity.Some lead a solitary existence; others live in communities;some have defined, geometric shapes; others have flexible

boundaries; some swim, some crawl, and some are seden-tary. Given these differences, it is perhaps surprising thatthere are only two types of cell (Fig. 1.9). Prokaryotic(Greek for “before nucleus”) cells have very little visibleinternal organization so that, for instance, the genetic mate-rial, stored in the molecule deoxyribonucleic acid (DNA),

IN DEPTH 1.2 MICROSCOPY REWARDED

Such has been the importance of microscopy to develop-ments in biology that two scientists have been awardedthe Nobel prize for their contributions to microscopy.Frits Zernike was awarded the Nobel prize for physics in1953 for the development of phase-contrast microscopywhilst Ernst Ruska received the same award in 1986 forthe invention of the transmission electron microscope.

Ruska’s prize marks one of the longest gaps betweena discovery (in the 1930s, in the research labs of theSiemens Corporation in Berlin) and the award of a Nobelprize. Anton van Leeuwenhoek died almost two centuriesbefore the Nobel prizes were introduced in 1901 and theprize is not awarded posthumously.


collagen fibers incross section

mitochondrion

cristae

lymphocyte

myeloid leukocyte

nucleus oflymphocyte

nuclearenvelope

basementmembrane

thick and thin filamentsin cross section

capillaryepithelial

(endothelial) cell

extracellular matrix

cardiacmuscle

cellcapillarybloodvessel

Figure 1.7. Transmission electron micrograph of a capillary blood vessel running between heart musclecells. Image by Giorgio Gabella, Department of Cell and Developmental Biology, University College London.Reproduced by permission.

is free within the cell. They are especially small, thevast majority being 1–2 μm in length. The prokaryotesare made up of two broad groups of organisms, thebacteria and the archaea (Fig. 1.10). The archaea wereoriginally thought to be an unusual group of bacteria butwe now know that they are a distinct group of prokaryoteswith an independent evolutionary history. The cells ofall other organisms, from yeasts to plants to worms tohumans, are eukaryotic (Greek for “with a nucleus”).These are generally larger (5–100 μm, although someeukaryotic cells are large enough to be seen with thenaked eye; see Fig. 1.1) and structurally more complex.Eukaryotic cells contain a variety of specialized structuresknown collectively as organelles, surrounded by a viscoussubstance called cytosol. Their DNA is held within thelargest organelle, the nucleus. The structure and functionof organelles will be described in detail in subsequentchapters. Table 1.1 summarizes the differences betweenprokaryotic and eukaryotic cells.

Cell Division

One of the major distinctions between prokaryotic andeukaryotic cells is their mode of division. In prokaryotesthe circular chromosome is duplicated from a singlereplication origin by a group of enzymes that reside onthe inside of the plasma membrane. At the completion ofreplication the old and new copies of the chromosomelie side by side on the plasma membrane, which thenpinches inwards between them. This process, whichgenerates two equal, or roughly equal, progeny cells isdescribed as binary fission. In eukaryotes the large, linearchromosomes, housed in the nucleus, are duplicated frommultiple origins of replication by enzymes located in thenucleus. Some time later the nuclear envelope breaksdown and the replicated chromosomes are compacted sothat they can be segregated without damage during mitosis.We will deal with mitosis in detail in Chapter 18. For themoment we should be aware that although it is primarilyabout changes to the nucleus, mitosis is accompanied by

VIRUSES 9

Individual Individual epithelial cellsepithelial cells

CiliaCilia

MicrovilliMicrovilli

Individual epithelial cells

Cilia

Microvilli

Figure 1.8. Scanning electron micrograph of airway epithelium. Image by GiorgioGabella, Department of Cell and Developmental Biology, University College London.Reproduced by permission.

TABLE 1.1. Differences between Prokaryotic and Eukaryotic Cells

Prokaryotes Eukaryotes

Size Usually 1–2 μm Usually 5–100 μm

Nucleus Absent Present, bounded by nuclear envelope

DNA Usually a single circular molecule(= chromosome)

Multiple linear molecules (chromosomes)a

Cell division Simple fission Mitosis or meiosis

Internal membranes Rare Complex (nuclear envelope, Golgi apparatus, endoplasmicreticulum, etc.)

Ribosomes 70Sb 80S (70S in mitochondria and chloroplasts)

Cytoskeleton Rudimentary Microtubules, microfilaments, intermediate filaments

Motility Rotary motor (drives bacterial flagellum) Dynein (drives cilia and flagella); kinesin, myosin

First appeared 3.5 × 109 years ago 1.5 × 109 years agoaThe tiny chromosomes of mitochondria and chloroplasts are exceptions; like prokaryotic chromosomes they are often circular.bThe S value, or Svedberg unit, is a sedimentation rate. It is a measure of how fast a molecule moves in a gravitational field, and therefore in anultracentrifuge.

dramatic changes to the organization of the rest of thecell. A new structure, the mitotic spindle, is assembledspecifically to move the chromosomes apart while otherstructures such as the Golgi apparatus and endoplasmicreticulum are dismantled so that their components canbe divided among the two progeny cells following celldivision.

VIRUSES

Viruses occupy a unique position between the living andnonliving worlds. On the one hand they are made of thesame molecules as living cells. On the other they are inca-pable of independent existence, being completely dependent


Nucleolus

Chromatin

Mitochondrion

Rough endoplasmic reticulum

Golgi apparatus

Plasma membrane

Plasmamembrane

Nucleus

A

B

Ribosomes

DNA

1 µm

Bacterium, prokaryotic

Animal cell, eukaryotic

10 µm

Figure 1.9. Organization of prokaryotic and eukaryotic cells.

on a host cell for reproduction. Almost all living organismshave viruses that infect them. Human viruses include polio,influenza, herpes, rabies, ebola, smallpox, chickenpox, andHIV (human immunodeficiency virus, the causative agentof AIDS). Viruses are submicroscopic particles consistingof a core of genetic material enclosed within a protein coatcalled the capsid. Some have an extra membrane layercalled the envelope. Viruses are metabolically inert untilthey enter a host cell, whereupon their genetic materialdirects the host cell machinery to produce viral protein andviral genetic material. Viruses often insert their genome intothat of the host, an ability that is widely made use of inmolecular biology research (Chapter 7). Bacterial viruses,bacteriophages, are used by scientists to transfer genesbetween bacterial strains. Human viruses are used as vehi-cles for gene therapy. By exploiting the natural infectioncycle of a virus such as adenovirus, it is possible to intro-duce a functional copy of a human gene into the cells ofa patient suffering from a genetic disease such as Lebercongenital amaurosis (page 333).

ORIGIN OF EUKARYOTIC CELLS

Prokaryotic cells are simpler in their organization thaneukaryotic cells and are assumed to be more primitive.According to the fossil record, prokaryotic organismsantedate, by at least 2 billion years, the first eukaryotesthat appeared some 1.5 billion years ago. It seemshighly likely that eukaryotes evolved from prokaryotes,and the most likely explanation of this process is theendosymbiotic theory. The basis of this theory is thatsome eukaryotic organelles originated as free-livingbacteria that were engulfed by larger cells in which theyestablished a mutually beneficial relationship. For example,mitochondria would have originated as free-living aerobicbacteria and chloroplasts as cyanobacteria, which arephotosynthetic prokaryotes formerly known as blue-greenalgae. The endosymbiotic theory provides an attractiveexplanation for the fact that mitochondria and chloroplastscontain their own DNA and ribosomes, both of which aremore closely related to those of bacteria than to all theother DNA and ribosomes in the same cell. The case for

CELL SPECIALIZATION IN ANIMALS 11

Bacteria Eukaryotes

ArchaeaProkaryotes

Last universal common ancestor

Vertebrates (mammals,birds, reptiles, fish...)

Arthropods(insects, spiders...)

Nematodes

Animals

Fungi(yeast, toadstools)

Green plants Ciliates

Viruses arose from many places on thistree as escaped bits of genome: theyare not living organisms.

end

osy

mbio

sis

tobec

om

e ch

loro

pla

sts

endosymbiosis tobecome mitochondria

Figure 1.10. The tree of life. The diagram shows the currently accepted view ofhow the different types of organism arose from a common ancestor. Many minor groupshave been omitted. Distance up the page should not be taken as indicating complexityor how ‘‘advanced’’ the organisms are. All organisms living today represent lineagesthat have had the same amount of time to evolve and change from the last universalcommon ancestor.

the origin of other eukaryotic organelles is less persuasive.Nevertheless, while it is clearly not perfect, most biologistsare now prepared to accept that the endosymbiotic theoryprovides at least a partial explanation for the evolution ofthe eukaryotic cell from prokaryotic ancestors.

CELL SPECIALIZATION IN ANIMALS

Animals are multicellular communities of individual cells.Lying between and supporting the cells is the extracellularmatrix (Fig. 1.7) of different types of fiber around which

the fluids and solute of the interstitial fluid can easily pass.All the body cells that comprise a single organism sharethe same set of genetic instructions in their nuclei (with thesingle exception of lymphocytes, page 317). Nevertheless,the cells are not all identical. Rather, they form a vari-ety of tissues, groups of cells that are specialized to carryout a common function. This specialization occurs becausedifferent cell types read out different parts of the DNAblueprint and therefore make different proteins. In animalsthere are four major tissue types: epithelium, connectivetissue, nervous tissue, and muscle. Some examples of thecells that make up these tissues are shown in Figure 1.11.


Motile neutrophil

Polarizedepithelialcell

Elongated nerve cell

Leading edge

Cell bodyAxon

Axon terminal

A

C

B

Figure 1.11. Different types of animal cells.

Epithelia are sheets of cells that cover the surface ofthe body and line its internal cavities such as the lungs andintestine. The cells may be columnar, taller than they arebroad (Fig. 1.11B), or squamous, meaning flat (e.g., thecapillary cell in Fig. 1.7). They are often polarized, mean-ing that one surface of the cell is distinct in its organization,composition and appearance from the other. In the intes-tine, the single layer of columnar cells lining the inside, orlumen, has an absorptive function that is increased by thefolding of the surface into villi (Fig. 1.12). The luminal sur-faces of these polarized cells have microvilli that increasethe surface area even further. The basal (bottom) surfacesits on a thin planar sheet of specialized extracellular matrixcalled the basement membrane or basal lamina. Many ofthe epithelial cells of the airways, for instance, those lin-ing the trachea and bronchioles, have cilia on their surfaces(Fig. 1.8). These are hairlike appendages that actively beatback and forth, moving a layer of mucus away from thelungs (Chapter 17). Particles and bacteria are trapped inthe mucus layer, preventing them from reaching the deli-cate air exchange membranes in the lung. In the case ofthe skin, the epithelium is said to be stratified because itis composed of several layers.

Connective tissues provide essential support for theother tissues of the body. They include bone, cartilage, andadipose (fat) tissue. Unlike other tissues, connective tis-sue contains relatively few cells within a large volume ofextracellular matrix that consists of different types of fiberembedded in amorphous ground substance (Fig. 1.12). Themost abundant of the fibers is collagen, a protein with the

tensile properties of steel that accounts for about a third ofthe protein of the human body. Other fibers have elasticproperties that permit the supported tissues to be displacedand then to return to their original position. The amor-phous ground substance absorbs large quantities of water,facilitating the diffusion of metabolites, oxygen, and carbondioxide to and from the cells in other tissues and organs.Of the many cell types found in connective tissue, two ofthe most important are fibroblasts, which make and secretethe ground substance and fibers, and macrophages, whichremove foreign, dead, and defective material. A number ofinherited diseases are associated with defects in connectivetissue. Marfan’s syndrome, for example, is characterized bylong arms, legs, and torso and by a weakness of the cardio-vascular system and eyes. These characteristics result froma defect in the organization of the collagen fibers.

Nervous tissue is a highly modified epithelium that iscomposed of several cell types. Principal among these arethe nerve cells, also called neurons (Fig. 1.11C), alongwith a variety of supporting cells that help maintain them.Neurons extend processes called axons, which can be over ameter in length. Neurons constantly monitor what is occur-ring inside and outside the body. They integrate and sum-marize this information and mount appropriate responses toit (Chapters 14–16). Another type of cell, glia, has otherroles in nervous tissue including forming the electrical insu-lation around axons.

Muscle tissue can be of two types, smooth or striated.Smooth muscle cells are long and slender and are usuallyfound in the walls of tubular organs such as the intestine and

STEM CELLS AND TISSUE REPLACEMENT 13

One villus

Red blood cell

Capillary

Smooth muscle cells orientated circularly

around intestine

Smooth muscle cells orientated longitudinally

along intestine (cut in cross section)

One microvillus

Nucleus

Basement membrane

Crypt

Epithelialcell

Connectivetissue

Fibroblast

Collagen fibers

Extracellularmatrix

Tight junction

Dividingstem cell

Figure 1.12. Tissues and structures of the intestine wall.

many blood vessels. In general, smooth muscle cells con-tract slowly and can maintain the contracted state for a longperiod of time. There are two classes of striated muscle:cardiac and skeletal. Cardiac muscle cells (Fig. 1.7) makeup the walls of the heart chambers. These are branchedcells that are connected electrically by gap junctions(page 46), and their automatic rhythmical contractionpowers the beating of the heart. Each skeletal muscle isa bundle of hundreds to thousands of fibers, each fiberbeing a giant single cell with many nuclei. This ratherunusual situation is the result of an event that occurs inthe embryo when the cells that give rise to the fibers fusetogether, pooling their nuclei in a common cytoplasm (theterm cytoplasm is historically a crude term meaning thesemi-viscous ground substance of cells; we use the term

to mean everything inside the plasma membrane exceptthe nucleus). The mechanism of muscle contraction willbe described in Chapter 17.

STEM CELLS AND TISSUEREPLACEMENT

Cells multiply by division. In the human body an estimated25 million cell divisions occur every second! These providenew cells for the blood and immune systems, for the repairof wounds and the replacement of dead cells. In complextissues such as those described above, division is restrictedto a small number of stem cells from which all of the othercells of the tissue derive. In the case of the intestine, folds in


the surface epithelium form crypts, each of which containsapproximately 250 cells (Fig. 1.12). Mature cells at the topdie and must be replaced by the division of between fourand six stem cells near the base of the crypt. Each stemcell divides roughly twice a day, the resulting cells movingup the crypt to replace those lost at the surface. Benign(noncancerous) polyps can be formed in the intestine if thisnormal balance between birth and death is disturbed.

As in the intestine, stem cells in other tissues existin specific locales, called niches, with environments thatsupport their special and vital functions. In many tissuesthe requirement to replace dead cells is much less than it isin the intestine and in such cases the stem cell niche mustmaintain its occupants in a quiescent (nondividing) stateuntil needed. Like stem cells themselves, the properties ofniches remain deeply mysterious. For the moment we havefew markers that allow us to specifically distinguish stem

cells from the cells around them and hence unambiguouslyidentify the territories they occupy. The resolution of suchquestions is vital if the potential of stem cells in cell therapyis to be realized.

THE CELL WALL

Many types of cell, particularly bacteria and plant cells,create a rigid case around themselves called a cell wall.For cells that live in an extracellular medium more dilutethan their own cytosol, the cell wall is critical in preventingthe cell bursting. For example, penicillin and many otherantibiotics block the synthesis of bacterial cell walls withthe result that the bacteria burst. Within trees, plant cellsmodify the cell wall to generate the woody trunk. Animalcells do not have cell walls.

IN DEPTH 1.3 STEM CELLS

Few developments in modern biology have had the med-ical and social impact that has followed the discovery ofstem cells. These are unspecialized cells from which allspecialized cells in the human body are derived. They arepresent in small numbers in almost all tissues and theycan either remain unspecialized for long periods, dividingat intervals to produce more stem cells (a process calledself-renewal) or they can differentiate into a wide vari-ety of specialized cell types. This means that stem cellshave enormous potential in what has become known asstem cell therapy. This involves treating patients suffer-ing from spinal cord injury or from a stroke, for example,with stem cells that have been preprogrammed to replacethe damaged tissue.

There are two kinds of stem cells: adult stem cellsand embryonic stem cells. It is the latter that has causedmuch of the controversy about stem cell therapy sincethey are derived from human embryos that are left overafter in vitro fertilization treatment. Cells from a four- tofive-day-old human embryo are pluripotent, that is, they

can be induced to create just about any cell type. Thereare fewer ethical objections to the use of adult stem cells,but as yet, these have nothing like the versatility of theirembryonic counterparts. Eventually it should be possibleto isolate stem cells from a patient and program theseappropriately before reintroducing them into the damagedtissue. Because they are the patient’s own cells, questionsof rejection and other complications do not arise.

In some respects, stem cell therapy is not really new.Bone marrow transplantation has been familiar in thetreatment of a variety of blood diseases for more than 40years. Patients suffering from cancers such as leukemiaand lymphoma, for example, receive doses of chemother-apy that kill the stem cells that are located in the bonemarrow. These give rise to the different cells in the blood;the red cells that carry oxygen around the body, the whitecells that help fight infection, and the platelets that helpblood clot. Replacement bone marrow, usually from ahealthy relative, is therefore essential to restock thesestem cells and allow the patient to make a full recovery.

AnswertoThoughtQuestion:Transmissionelectronmicroscopy.Iftheappropriatefluorescentdyesareusedlightmicro-scopescanrevealthelocationoftheGolgicomplexwithinacell,butonlytheelectronmicroscopehassufficientresolutiontoshowthestructureoftheorganelleandhencewhetheritismalformed.MalformationoftheendoplasmicreticulumandGolgiapparatusisthoughttounderlieonetypeofinheritedspasticparaplegia�.

REVIEW QUESTIONS 15

SUMMARY

1. All living organisms are made of cells.

2. Our understanding of cell structure and function hasgone hand in hand with developments in microscopyand its associated techniques.

3. Light microscopy revealed the diversity of cell typesand the existence of the major organelles such as thenucleus and mitochondria.

4. The electron microscope reveals the detailed struc-ture of the larger organelles and resolves the cellultrastructure, the fine detail, at the nanometer scale.

5. There are only two types of cells, prokaryotic andeukaryotic.

6. Prokaryotic cells have little visible internal organi-zation. They are usually 1–2 μm in size.

7. Eukaryotic cells usually measure 5–100 μm. Theycontain a variety of specialized internal organelles,the largest of which, the nucleus, contains the geneticmaterial.

8. The endosymbiotic theory proposes that someeukaryotic organelles, such as mitochondria andchloroplasts, originated as free-living prokaryotes.

9. In multicellular organisms, cells are organized intotissues. In animals there are four tissue types: epithe-lium, connective tissue, nervous tissue, and muscle.

10. The extracellular matrix is found on the outside ofanimal cells.

11. In tissues, specialized cells arise from unspecializedstem cells.

FURTHER READING

Booth, C., and Potten, C. S. (2000) Gut instincts: thoughts onintestinal epithelial stem cells. Journal of Clinical Investigation105, 1493–1499.

Gest, H. (2004) The discovery of microorganisms by RobertHooke and Antoni van Leeuwenhoek, Fellows of the Royal

Society. Notes and Records of the Royal Society of London, 58,187–201.

Harris, H. (1999) The Birth of the Cell , Yale University Press,New Haven, Connecticut.

REVIEW QUESTIONS

We use the same format of review questions throughoutthe book. For each of the numbered questions choose thebest response from the lettered list. The same response mayapply to more than one numbered question. Unless specifi-cally told to do so, you should not refer back to the chaptertext or figures in answering the questions. Answers are atthe back of the book, starting on page 381.

1.1 Theme: Dimensions in Cell Biology

A 0.025 nm

B 0.2 nm

C 20 nm

D 250 nm

E 2,000 nm

F 20,000 nm

G 200,000 nm

H 5,000,000 nm

I 1,000,000,000 nm

J 20,000,000,000 nm

From the above list, select the dimension most appropriatefor each of the descriptions below.

1. A typical bacterium2. A typical eukaryotic cell3. The longest cell in the human body4. Resolution of a light microscope5. Resolution of a transmission electron microscope

1.2 Theme: Types of Cell

A bacterium

B epithelial cell

C fibroblast

D macrophage

E glial cell

F skeletal muscle cell

G stem cell


From the above list of cell types, select the cell corresponding to each of the descriptions below.

1. A cell that synthesizes collagen2. A cell type found in nervous tissue3. A cell type that forms sheets, e.g., to separate different spaces in the body4. A cell whose role is to remove dead and foreign material5. A cell with no nuclear envelope6. Large cells with multiple nuclei7. Undifferentiated cells capable of multiple rounds of cell division

1.3 Theme: Some Basic Components of the Eukaryotic CellB

A

C

D

E

F

G

Identify each of the cellular components below from the figure above.

1. Cytosol2. Internal membranes3. Mitochondrion4. Nucleus5. Plasma membrane

THOUGHT QUESTION

Each chapter has a thought question. For these you areencouraged to refer back to the text and diagrams withinthe chapter to formulate your response. Answers appearearlier in the relevant chapter, printed upside down.

You wish to test the hypothesis that a particular inher-ited human disease is characterized by malformation of theGolgi apparatus. What type of microscopy would you useto examine a tissue biopsy from a patient?

cells and tissues - wiley · 2019. 12. 28. · 1 cells and tissues the cell is the basic unit of...

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